Sex Differences in Patients With Chronic Heart Failure With Reference to Left Ventricular Ejection Fraction

Background: Data on sex differences in heart failure (HF) with reference to left ventricular ejection fraction (LVEF) are limited. Methods and Materials: We examined 4683 consecutive patients (mean 69 years) with HF in the CHART-2 study. Results: Compared to men (N = 3188), women with HF (N = 1495) were older and had a lower prevalence of ischemic heart disease and cancer, received less implementation of evidence-based treatment, and were characterized by more severe HF in terms of higher New York Heart Association (NYHA) functional class and increased brain natriuretic peptide (BNP) levels, despite greater preservation of LVEF. During the median 6.3-year follow-up, all-cause mortality was comparable between women and men (32.8% vs 33.2%, P = .816), while women had higher cardiovascular mortality, particularly among those with LVEF ≥50%. Although no sex differences existed in cause of death among patients with LVEF ≤ 40% and 41% to 49%, women had a higher proportion of cardiovascular death and lower proportion of noncardiovascular death than men among those with LVEF ≥ 50%. Multivariable Cox regression models showed that women with HF had reduced risk of both cardiovascular and noncardiovascular death, regardless of LVEF category. Beta-blockers were associated with improved mortality in women but not men with LVEF ≤ 40%, while renin–angiotensin system inhibitors were not associated with improved mortality in women with LVEF ≥ 50% but were in men. Conclusion: In addition to sex-specific differences in the age of onset, etiology and response to treatment, women with heart failure and preserved left ventricular ejection fraction (LVEF ≥ 50%) have higher cardiovascular mortality than men. Sex-related management of congestive heart failure should include a consideration of LVEF

Adult Living Donor Liver Transplantation for Patients With Portal Vein Thrombosis: A Single-center Experience

Background. Living donor liver transplantation (LDLT) for patients with portal vein thrombosis (PVT) is associated with several technical challenges for its complicated procedures and poor outcomes. Some institutions still consider preexisting PVT as a relatively contraindication for LDLT. Methods. Between April 2010 and May 2016, 129 adults underwent LDLT at our institution, and 28 (21.7%) of whom had preexisting PVT. Portal vein thrombosis was diagnosed using preoperative imaging techniques and intraoperative findings. The characteristics and outcomes of the cases were retrospectively evaluated. Results. The type of PVT included Yerdel grade 1 in 21 (75.0%) cases, grade 2 in 3 (10.7%) cases, and grade 3 in 4 (14.3%) cases. There were no cases of Yerdel grade 4 PVT. After removing thrombus inside the vessel, we performed simple portal vein anastomosis in 25 (89.3%) cases, patch technique with vascular graft in 1 case (3.6%), and an interposition technique with vascular graft in 2 cases (7.1%). Compared with the non-PVT group, cold ischemic time was longer (P = 0.012) and the rate of postoperative PVT was higher (P = 0.001) in PVT group. In the comparison between the recipient without and with postoperative PVT, the existence of preoperative PVT was the independent risk factor in the multivariate analysis (hazard ratio, 7.511; 95% confidence interval 1.382-40.820; P = 0.020). Conclusions. Although it had a technically complicated operation, LDLT could be safely performed in the patients with PVT in our institution

High Incidence of C797S Mutation in Patients With Long Treatment History of EGFR Tyrosine Kinase Inhibitors Including Osimertinib

Introduction: Although treatment with osimertinib confers survival benefits in patients with lung cancer with the EGFR T790M mutation, the mechanism of acquired resistance to osimertinib remains poorly understood. We conducted a prospective observational study to identify the mechanism on the basis of repeated tissue biopsies. Methods: Patients with EGFR-mutated advanced lung cancer with a T790M mutation detected on a tissue biopsy underwent a rebiopsy after developing acquired resistance to osimertinib. Nucleic acids extracted from the biopsy samples were subjected to targeted resequencing (Oncomine Comprehensive Assay), and circulating cell-free DNA (ccfDNA) was analyzed by CAncer Personalized Profiling by deep Sequencing (AVENIO ctDNA Surveillance Kit). Results: Between November 2016 and March 2020, a total of 87 patients were screened. Among them, 44 developed acquired resistance. Of these, 19 samples from rebiopsies and 12 from preosimertinib biopsies were able to be analyzed by an Oncomine Comprehensive Assay. A ccfDNA analysis was performed in 16 patients. Regarding the mechanisms of acquired resistance, structural change in EGFR, namely, C797S, G796S, or L792V, was the most frequent alteration, being observed in 57.9% of the cases. MET gain was observed in 31.6% of the cases, and gains in cell cycle genes were observed in 26.3% of the cases. In addition, we identified GAS6 gain and an ATM mutation in a patient with small-cell transformation and a BRAF V600E mutation in a patient with oligoprogressive disease. Conclusions: A repeated tissue biopsy and a ccfDNA analysis were useful in analyzing the mechanisms underlying acquired resistance. A long treatment history of EGFR TKIs may result in a high percentage of EGFR structural change